Research based on the dopamine hypothesis of schizophrenia has led to the discovery of many dopamine-rich areas in limbic forebrain associated with the biochemical substrate of schizophreniform behaviors. Many of these dopamine neurons contain the sulfated form of cholecystokinin octapeptide (CCK- 8S). There is growing evidence that CCK-8S may be a neuromodulator or a neurotransmitter in these dopaminergic neurons. In order for CCK-8S to satisfy the criteria for a neurotransmitter or neuromodulator, its action in the synapse must be terminated or temporally limited. The behavioral action of CCK-8S and binding of CCK-8S to its receptor are dependent upon the presence of a sulfated tyrosine residue on the CCK molecule. We hypothesize the existence of a synaptic arylsulfatase which terminates the action of CCK-8S by removing the sulfate group from the tyrosine residue. This enzyme may be associated with the biochemical substrate of schizophreniform behaviors arising from limbic forebrain. This study is designed to begin testing this hypothesis by addressing the following specific aims: (1) partially purify and characterize arylsulfatase activity of limbic forebrain with artificial substrate comparing with commercially available arylsulfatase preparations; (2) determine kinetic parameters of arylsulfatase using CCK-8s as substrate, comparing purified with commercially available arysulfatase preparations; (3) determine modulating effects of drugs and other compounds on arylsulfatase activity. The discovery that neuropeptides such as cholecystokinin co-exist in the same neuronal termini as dopamine has led to modification of the original dopamine hypothesis of schizophrenia proposed by Meltzer and Stahl in 1976. Given the interactions of dopamine and cholecystokinin in the limbic system, basic knowledge about this potential biochemical substrate of schizophrenic behaviors is pivotal to understanding the etiology of this disease.